ProQR Therapeutics has reported that their drug sepofarsen failed to meet its primary and secondary endpoints in recent Phase II/III clinical trials.
ProQR Therapeutics has reported that its trial of drug sepofarsen failed to meet the primary and secondary endpoints in recent Phase II/III clinical trials. The therapeutic was intended to treat CEP290-mediated Leber congenital amaurosis 10 (LCA10), an inherited retinal disorder that results in several visual impairment or blindness.
The results were unexpected as the company reported positive data following its Phase I clinical trial. Early study results from 11 participants indicated that the drug was able to improve visual acuity, light sensitivity and the ability to navigate an obstacle course, with some participants experiencing substantial changes in vision. Improvement in visual ability in Phase I trials was seen as early as two months after beginning treatment and proved to be stable.
However, ProQR has reported that in 36 participants from Phase II/III trials, patients who were treated with sepofarsen did not experience a significant change in best corrected visual acuity, the primary endpoint of the trial, at the 12-month follow-up in comparison to the placebo group. There was also no difference between the treatment and placebo group in a full-field stimulus test, a measure of sensitivity of the entire visual field, or mobility. The drug was generally well-tolerated.
“Given the results observed in earlier studies of sepofarsen, the Illuminate trial results are unexpected and disappointing, especially for people living with LCA10,” said Daniel A. de Boer, Founder and CEO of ProQR Therapeutics. “ProQR was founded with the goal of developing RNA therapies for patients with high unmet medical need, and we will continue to advance our robust pipeline of therapies for genetic eye disease. We are deeply grateful to all of the participants, their supporters, and investigators who participated in the Illuminate study.”
Sepofarsen is an antisense oligonucleotide therapy. Antisense oligonucleotides are short, synthetic and chemically modified chains of nucleotides that are able to target any gene product of interest and translate DNA code into proteins. Sepofarsen specifically targets the gene CEP290, which is mutated in people with LCA10 and causes improper RNA splicing. Sepofarsen works by binding the mutated RNA and corrects splicing, allowing the retina to produce the protein again, helping to restore visual capabilities.
Although ProQR has not committed to running another trial of sepofarsen in the treatment of LCA10, the company is working on several other antisense oligonucleotide therapies for retinal diseases. Ultevursen is intended for the treatment of retinitis pigmentosa and Usher Syndrome, inherited retinal diseases that cause severe vision loss. Promising results were reported from Phase I/II studies showing benefits in multiple vision tests and Phase II/III trials are ongoing. ProQR is also testing therapeutic QR-504a in Phase I clinical trials, a drug intended for the treatment of Fuchs endothelial corneal dystrophy.
Leber congenital amaurosis 10 has no current treatments or cures for patients with the condition. Beyond ProQR’s trials, Editas Medicine is currently recruiting for Phase I clinical trials to determine the efficacy of EDIT-101 in people with LCA10. EDIT-101 is a CRISPR-based experimental drug that delivers gene-editing machinery directly to photoreceptor cells.
